Drug safety concerns

This study will seek to determine if the downstream effects of cyclooxygenase-2 (COX-2) inhibition suggested by preclinical systems occur in human prostate cancer. To answer this question, men who have chosen prostatectomy will be randomly assigned to preoperative treatment with celecoxib or placebo for four weeks. Carefully collected tumor, premalignant, and benign prostate tissue will then be examined for apoptosis, androgen receptor and prostaglandin E2 levels. Tumor COX-2 expression will be correlated with observed treatment effects. The data generated by this study will serve as a foundation for the development of COX-2 targeted therapies for prostate cancer, will provide preliminary evidence for larger scale clinical trials aimed at treatment and prevention of prostate cancer, and will validate current preclinical models used to study COX-2 in prostate cancer.

PRIMARY OBJECTIVE

I. To determine if COX-2 inhibition with celecoxib significantly increases apoptosis in human adenocarcinoma of the prostate.

SECONDARY OBJECTIVES

I. To determine if COX-2 inhibition with celecoxib reduces levels of Prostaglandin E2 and androgen receptor in fresh tumor tissue collected at prostatectomy

II. To collect pre- and postoperative serum Prostate Specific Antigen (PSA) for exploratory analyses

III. To determine the effect of celecoxib on adverse effects, perioperative surgical complications and post surgery analgesic use

Inclusion Criteria:

• Histopathologically or cytologically proven adenocarcinoma of the prostate and planned prostatectomy
• Age >= 18
• Performance status (ECOG <= 2)
• Hemoglobin > 10 g/dL (within 4 weeks)
• Creatinine <= 1.5 mg/dL
• Signed informed patient consent

Exclusion Criteria:

• Other preoperative or prior treatment directed at prostate cancer
• Significant active medical illness which in the opinion of the investigator would preclude protocol treatment
• Use of non-steroidal anti-inflammatory agents within seven days of celecoxib treatment
• Hypersensitivity to celecoxib
• A history of asthma, urticaria, or anaphylaxis precipitated by an NSAID
• History of significant upper gastrointestinal bleeding or active peptic ulcer disease
• Current treatment with anticoagulants
• Allergy to sulfonamide